CHMP Recommends Tislelizumab for First-Line Therapy in Advanced Gastric and Esophageal Cancers

BeiGene has received positive opinions from the European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) for its drug tislelizumab as a first-line treatment for two major cancers: gastric or gastroesophageal junction (G/GEJ) cancer and esophageal squamous cell carcinoma (ESCC). These recommendations are based on two key phase 3 clinical trials, RATIONALE-305 and RATIONALE-306, which demonstrated significant overall survival benefits when tislelizumab was used in combination with chemotherapy.

In the case of G/GEJ adenocarcinoma, the RATIONALE-305 trial evaluated the efficacy of tislelizumab combined with platinum- and fluoropyrimidine-based chemotherapy in 997 patients. The study showed that patients receiving the tislelizumab combination had a median overall survival (OS) of 15 months, compared to 12.9 months in the placebo group, translating to a 20% reduction in the risk of death (HR: 0.80, P = .0011). Patients whose tumors expressed PD-L1 with a TAP score ≥5% saw an even more pronounced OS benefit, with median survival reaching 16.4 months versus 12.8 months for the placebo group, a 29% reduction in the risk of death.

For ESCC, the RATIONALE-306 study involved 649 patients treated with tislelizumab in combination with platinum-based chemotherapy. Results showed a median OS of 17.2 months for the tislelizumab arm, compared to 10.6 months for those on placebo, marking a 34% reduction in the risk of death (HR: 0.66, P <.0001). Patients with PD-L1 expression (TAP score ≥5%) saw even greater benefit, with a median OS of 19.1 months compared to 10.0 months in the placebo group, reflecting a 38% reduction in the risk of death.

Tislelizumab’s safety profile was consistent with previous studies, with common grade 3 or 4 adverse reactions including neutropenia, anemia, fatigue, and pneumonia. The safety data reviewed by CHMP included over 1,500 patients treated with tislelizumab monotherapy or in combination with chemotherapy for G/GEJ cancer, ESCC, or non-small cell lung cancer (NSCLC).

Tislelizumab is already approved in the EU for certain indications in ESCC and NSCLC. The positive CHMP opinions for these new first-line indications in G/GEJ cancer and ESCC position tislelizumab as a promising treatment option that could further improve survival outcomes for patients with advanced gastric, gastroesophageal, and esophageal cancers.